Aryl triazines as LPAAT-SS inhibitors and uses thereof

A method for reducing the activity of lysophosphatidic acid acyltransferase β (LPAAT-β) comprising contacting LPAAT-β with a compound or salt thereof, or in combination with a pharmaceutically acceptable carrier or diluent, in an amount effective to reduce LPAAT-β activity, wherein the compound has the formula:

• 98
• wherein:
• Q is NH, N—(CH2)n, (CH2)n—N, O, O—(CH2)n, (CH2)n—O, S, S—(CH2)n or (CH2)n—S, where n is 1-10;
• R1 is H, OH, alkyl, alkoxy, Cl, F, Br, CR3 where R3 is Cl3, F3 or Br3, NH2, NHR or NRR′ where R and R′ independently are alkyl;
• R2 is H, OH, alkyl, alkoxy, Cl, F, Br or CR3 where R3 is Cl3, F3 or Br3;
• R3 is H, alkyl, alkoxy, Cl, CCl3, C≡N, NH2, NHR, NRR′ or SR where R and R′ independently are alkyl, or R and R′ are joined together to form a ring with the N;
• R4 and R5 are independently H, OH, alkyl, alkenyl, alkynyl, alkoxy, (CH2)n—OR where R is H or alkyl and n is 1-10, Cl, F, Br, CR3 where R3 is Cl3, F3 or Br3, acyl, heterocycle, N+(50 O)O−, C≡N, N3, SH, SR where R is alkyl, NH2, NHR or NRR′ where R and R′ independently are alkyl or are joined together to form a ring with the N, or R4 and R5 are taken together with the benzene ring to form a heterocycle or R4 and R5 are independently alkyl or alkenyl and joined together to form a ring with the two carbon atoms of the benzene ring to which R4 and R5 are attached;
• and
• with the proviso that R1 and R2 are not both Cl where R3 is NH2 and Q is N.

A method for inhibiting the proliferation of a cell in which the activity of lysophosphatidic acid acyltransferase β (LPAAT-β) is required for the proliferation of the cell comprising contacting the cell with a compound or salt thereof, or in combination with a pharmaceutically acceptable carrier or diluent, in an amount effective to inhibit the proliferation of the cell, wherein the compound has the formula:

• 99
• wherein:
• Q is NH, N—(CH2)n, (CH2)n—N, O, O—(CH2)n, (CH2)n—O, S, S—(CH2)n or (CH2)n—S, where n is 1-10;
• R1 is H, OH, alkyl, alkoxy, Cl, F, Br, CR3 where R3 is Cl3, F3 or Br3, NH2, NHR or NRR′ where R and R′ independently are alkyl;
• R2 is H, OH, alkyl, alkoxy, Cl, F, Br or CR3 where R3 is Cl3, F3 or Br3;
• R3 is H, alkyl, alkoxy, Cl, CCl3, C≡N, NH2, NHR, NRR′ or SR where R and R′ independently are alkyl, or R and R′ are joined together to form a ring with the N;
• R4 and R5 are independently H, OH, alkyl, alkenyl, alkynyl, alkoxy, (CH2)n—OR where R is H or alkyl and n is 1-10, Cl, F, Br, CR3 where R3 is Cl3, F3 or Br3, acyl, heterocycle, N+(═O)O−, C≡N, N3, SH, SR where R is alkyl, NH2, NHR or NRR′ where R and R′ independently are alkyl or are joined together to form a ring with the N, or R4 and R5 are taken together with the benzene ring to form a heterocycle or R4 and R5 are independently alkyl or alkenyl and joined together to form a ring with the two carbon atoms of the benzene ring to which R4 and R5 are attached;
• and
• with the proviso that R1 and R2 are not both Cl where R3 is NH2 and Q is N.

A method for treating a cancer in which lysophosphatidic acid acyltransferase β (LPAAT-β) activity is associated comprising administering to an animal in need, a compound or salt thereof, or in combination with a pharmaceutically acceptable carrier or diluent, in an amount effective to treat the cancer, wherein the compound has the formula:

• 100
• wherein:
• Q is NH, N—(CH2)n, (CH2)n—N, O, O—(CH2)n, (CH2)n—O, S, S—(CH2)n or (CH2)n—S, where n is 1-10;
• R1 is H, OH, alkyl, alkoxy, Cl, F, Br, CR3 where R3 is Cl3, F3 or Br3, NH2, NHR or NRR′ where R and R′ independently are alkyl;
• R2 is H, OH, alkyl, alkoxy, Cl, F, Br or CR3 where R3 is Cl3, F3 or Br3;
• R3 is H, alkyl, alkoxy, Cl, CCl3, C≡N, NH2, NHR, NRR′ or SR where R and R′ independently are alkyl, or R and R′ are joined together to form a ring with the N;
• R4 and R5 are independently H, OH, alkyl, alkenyl, alkynyl, alkoxy, (CH2)n—OR where R is H or alkyl and n is 1-10, Cl, F, Br, CR3 where R3 is Cl3, F3 or Br3, acyl, heterocycle, N+(═O)O−, C≡N, N3, SH, SR where R is alkyl, NH2, NHR or NRR′ where R and R′ independently are alkyl or are joined together to form a ring with the N, or R4 and R5 are taken together with the benzene ring to form a heterocycle or R4 and R5 are independently alkyl or alkenyl and joined together to form a ring with the two carbon atoms of the benzene ring to which R4 and R5 are attached;
• and
• with the proviso that R1 and R2 are not both Cl where R3 is NH2 and Q is N.

A coated medical device for inhibiting the proliferation of a cell in which the activity of lysophosphatidic acid acyltransferase β (LPAAT-β) is required for the proliferation of the cell comprising a medical device coated with a compound or salt thereof, or in combination with a pharmaceutically acceptable carrier or diluent, in an amount effective to inhibit the proliferation of the cell, wherein the compound has the formula:

• 101
• wherein:
• Q is NH, N—(CH2)n, (CH2)n—N, O, O—(CH2)n, (CH2)n—O, S, S—(CH2)n or (CH2)n—S, where n is 1-10;
• R1 is H, OH, alkyl, alkoxy, Cl, F, Br, CR3 where R3 is Cl3, F3 or Br3, NH2, NHR or NRR′ where R and R′ independently are alkyl;
• R2 is H, OH, alkyl, alkoxy, Cl, F, Br or CR3 where R3 is Cl3, F3 or Br3;
• R3 is H, alkyl, alkoxy, Cl, CCl3, C≡N, NH2, NHR, NRR′ or SR where R and R′ independently are alkyl, or R and R′ are joined together to form a ring with the N;
• R4 and R5 are independently H, OH, alkyl, alkenyl, alkynyl, alkoxy, (CH2)n—OR where R is H or alkyl and n is 1-10, Cl, F, Br, CR3 where R3 is Cl3, F3 or Br3, acyl, heterocycle, N+(═O)O−, C≡N, N3, SH, SR where R is alkyl, NH2, NHR or NRR′ where R and R′ independently are alkyl or are joined together to form a ring with the N, or R4 and R5 are taken together with the benzene ring to form a heterocycle or R4 and R5 are independently alkyl or alkenyl and joined together to form a ring with the two carbon atoms of the benzene ring to which R4 and R5 are attached;
• and
• with the proviso that R1 and R2 are not both Cl where R3 is NH2 and Q is N.